Lactate Dehydrogenase-Elevating Virus Induces Systemic Lymphocyte Activation via TLR7-Dependent IFNα Responses by Plasmacytoid Dendritic Cells
Open Access
- 1 July 2009
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 4 (7), e6105
- https://doi.org/10.1371/journal.pone.0006105
Abstract
Lactate dehydrogenase-elevating virus (LDV) is a natural infectious agent of mice. Like several other viruses, LDV causes widespread and very rapid but transient activation of both B cells and T cells in lymphoid tissues and the blood. The mechanism of this activation has not been fully described and is the focus of the current studies. A known inducer of early lymphocyte activation is IFNα, a cytokine strongly induced by LDV infection. Neutralization of IFNα in the plasma from infected mice ablated its ability to activate lymphocytes in vitro. Since the primary source of virus-induced IFNα in vivo is often plasmacytoid dendritic cells (pDC's), we depleted these cells prior to LDV infection and tested for lymphocyte activation. Depletion of pDC's in vivo eradicated both the LDV-induced IFNα response and lymphocyte activation. A primary receptor in pDC's for single stranded RNA viruses such as LDV is the toll-like receptor 7 (TLR7) pattern recognition receptor. Infection of TLR7-knockout mice revealed that both the IFNα response and lymphocyte activation were dependent on TLR7 signaling in vivo. Interestingly, virus levels in both TLR7 knockout mice and pDC-depleted mice were indistinguishable from controls indicating that LDV is largely resistant to the systemic IFNα response. Results indicate that LDV-induced activation of lymphocytes is due to recognition of LDV nucleic acid by TLR7 pattern recognition receptors in pDC's that respond with a lymphocyte-inducing IFNα response.Keywords
This publication has 33 references indexed in Scilit:
- Exhaustion of Type I Interferon Response following an Acute Viral InfectionThe Journal of Immunology, 2006
- Type I Interferons Trigger Systemic, Partial Lymphocyte Activation in Response to Viral InfectionThe Journal of Immunology, 2005
- Identification of a Novel Coronavirus in Patients with Severe Acute Respiratory SyndromeNew England Journal of Medicine, 2003
- Links between innate and adaptive immunity via type I interferonCurrent Opinion in Immunology, 2002
- Lactate dehydrogenase-elevating virus (LDV): lifelong coexistence of virus and LDV-specific immunity.The Journal of Immunology, 1997
- Persistent infection of mice by lactate dehydrogenase-elevating virus: effects of immunosuppression on virus replication and antiviral immune responsesVirus Research, 1989
- Replication of Lactate Dehydrogenase-elevating Virus in Macrophages: 1. Evidence for Cytocidal ReplicationJournal of General Virology, 1982
- Inhibition of Cellular Immune Reactions in Mice infected with Lactic Dehydrogenase VirusNature, 1969
- Infection of Tumor-Bearing Mice with the Lactic Dehydrogenase AgentExperimental Biology and Medicine, 1962
- Virus interference. I. The interferonProceedings of the Royal Society of London. Series B - Biological Sciences, 1957